CREB required for the stability of new and reactivated fear memories
CREB required for the stability of new and reactivated fear memories
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DOI：
10.1038/nn819
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发表时间：
2002-04-01
影响因子：
25
通讯作者：
Silva, AJ
中科院分区：
文献类型：
--
作者：
Kida, S;Josselyn, SA;Silva, AJ
cAMP反应元件结合蛋白（CREB）家族的转录因子被认为是记忆形成的关键。为了确定CREB在不同的记忆过程中的作用，我们通过将CREBS133A融合到雌激素受体配体结合结构域（LBD）的他莫昔芬（TAM）依赖性突变体来获得具有可诱导和可逆CREB阻遏物的转基因小鼠。我们发现CREB对长期条件性恐惧记忆的巩固至关重要，但对这些记忆的编码、存储或检索却不起作用。我们的研究还表明，CREB是重新激活或恢复的条件性恐惧记忆的稳定所必需的。虽然初始和重新激活的记忆的稳定性所必需的转录过程不同，但CREB对两者都是必需的。本文的研究结果描述了需要CREB的记忆过程，并证明了LBD诱导的转基因系统在复杂认知过程研究中的作用。
The cAMP-responsive element binding protein (CREB) family of transcription factors is thought to be critical in memory formation. To define the role of CREB in distinct memory processes, we derived transgenic mice with an inducible and reversible CREB repressor by fusing CREBS133A to a tamoxifen (TAM)-dependent mutant of an estrogen receptor ligand-binding domain (LBD). We found that CREB is crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories. Our studies also showed that CREB is required for the stability of reactivated or retrieved conditioned fear memories. Although the transcriptional processes necessary for the stability of initial and reactivated memories differ, CREB is required for both. The findings presented here delineate the memory processes that require CREB and demonstrate the power of LBD-inducible transgenic systems in the study of complex cognitive processes.